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High levels of Lymphotoxin-Beta (LT-Beta) gene expression in rheumatoid arthritis synovium: clinical and cytokine correlations

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Abstract

Lymphotoxin-Beta (LT-Beta) is implicated in lymphoid follicle development, production of pro-inflammatory cytokines, and can enhance the proliferation of fibroblasts and synoviocytes. The objective of this study was to investigate LT-Beta and LT-BetaReceptor (LT-BetaR) gene expression in RA patient synovium and blood samples compared with control individuals, and correlate with LT-Alpha and TNF-Alpha gene expression and disease parameters. RT-PCR was used to investigate the gene expression of LT-Beta, LT-BetaR, TNF-Alpha and LT-Alpha in the blood and synovium of RA patients and a control group of individuals. LT-Beta gene expression was significantly higher in RA patient synovium compared to control synovium (P = 0.005). There was a significant positive correlation between LT-Beta and LT-Alpha gene expression in both the synovium (P = 0.001) and blood (P = 0.002) of RA patients. LT-Beta gene expression was significantly higher in RA patient synovial samples that were inflamed to a moderately severe degree compared to those inflamed to a minimal degree (P = 0.02). Analysis of clinical variables revealed a significant positive correlation between LT-BetaR gene expression in RA patient synovium and Pain VAS Score (P = 0.01) and also HAQ Score (P = 0.01). Increased LT-Beta gene expression occurs in RA synovium and correlates with the degree of inflammation. LT-Beta may play a role in RA disease pathogenesis by contributing to a more intense inflammatory reaction in the synovium.

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Acknowledgments

This work was supported by ICARE (Irish Center for Arthritis Research and Education). We would like to thank Pat Higgins and Liam Burgess, Microbiology department for their technical assistance, Kathleen O` Sullivan for statistical support, colleagues in the department of Orthopaedic Surgery and Pathology, Cork Regional Hospital for acquisition and analysis of synovial biopsies, and participating patients for their consent in facilitating this study.

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Authors and Affiliations

  1. Department of Microbiology, Biomerit Research Center, University College Cork, Cork, Ireland

    Killian P. O’Rourke, G. O’Donoghue, C. Adams, H. Mulcahy, C. Molloy & F. O’Gara

  2. Department of Rheumatology, Cork Regional Hospital, Cork, Ireland

    C. Silke & M. Molloy

  3. Department of Medicine, Cork Regional Hospital, Cork, Ireland

    F. Shanahan

  4. Department of Rheumatology, Musgrove Park Hospital, Taunton, Somerset, TA1 5DA, UK

    Killian P. O’Rourke

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  1. Killian P. O’Rourke
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  2. G. O’Donoghue
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  3. C. Adams
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  4. H. Mulcahy
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  5. C. Molloy
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  7. M. Molloy
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  8. F. Shanahan
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  9. F. O’Gara
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Correspondence to Killian P. O’Rourke.

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O’Rourke, K.P., O’Donoghue, G., Adams, C. et al. High levels of Lymphotoxin-Beta (LT-Beta) gene expression in rheumatoid arthritis synovium: clinical and cytokine correlations. Rheumatol Int 28, 979–986 (2008). https://doi.org/10.1007/s00296-008-0574-z

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  • DOI: https://doi.org/10.1007/s00296-008-0574-z

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